A Phase3 Study to Evaluate the Efficacy and Safety of MEDI3250 in Healthy Japanese Children Age 7 Years Through 18 Years: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase3 Study to Evaluate the Efficacy and Safety of MEDI3250 in Healthy Japanese Children Age 7 Years Through 18 Years (NCT02269475), a randomized phase 3 study. The primary outcome is the Incidence of Laboratory-confirmed Influenza Infection (Matched Strain).

2. Clinical Question

The trial was designed to gather efficacy, safety and tolerability data in Japanese children. Its primary outcome is a participant count: children with a laboratory-confirmed infection from a strain matched to the vaccine. The record reports zero such events among 849 MEDI3250 participants and one among 430 placebo participants in the primary analysis population.

The registry also reports infection from any strain as a secondary outcome. That broader measure includes infections not restricted to matched strains, so it addresses a different question. The posted results therefore allow the primary matched-strain outcome to be considered alongside a broader secondary outcome, while keeping their distinct definitions in view. Neither result alone describes every aspect of vaccine efficacy, safety or tolerability.

3. Trial Design

This was a Phase 3, randomized, double-blind, parallel-group study of MEDI3250 compared with placebo. The registry lists healthy Japanese children aged 7 years through 18 years as the study population. The study is recorded as completed, with enrollment of 1369. Random allocation and double masking are features intended to limit systematic differences in treatment assignment and knowledge of assigned treatment; the registry record does not report further details about how these procedures were implemented.

The intervention was MEDI3250 nasal spray, and the comparator was placebo nasal spray. The primary endpoint was the incidence of laboratory-confirmed influenza infection caused by a matched strain. It was assessed through the end of the influenza surveillance period, up to end Apr (6 months), in the Per Protocol Population. The registry describes the primary outcome as a number of participants, rather than a continuous measurement or a time-to-event estimate.

The posted primary analysis compares 849 participants in the MEDI3250 group with 430 in the placebo group. Those analysis counts are not the same as the safety counts: the adverse-event record lists 868 at risk in the MEDI3250 group and 433 in the placebo group. These counts refer to different reported analysis contexts and should not be treated as interchangeable.

The registry lists two secondary outcomes, including laboratory-confirmed infection from any strain and infection from matched strains by strain. It also reports safety events. Details such as the randomization procedure, allocation concealment, masking procedures, sample-size justification and planned interim analyses are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per Protocol Population

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as the Incidence of Laboratory-confirmed Influenza Infection (Matched Strain), measured over through the end of the influenza surveillance period, up to end Apr (6 months).

The primary endpoint counts participants with laboratory-confirmed influenza infection caused by a strain matched to the vaccine during the surveillance period. Laboratory confirmation applies a defined diagnostic criterion, while the matched-strain restriction focuses the endpoint on infections from strains considered relevant to the vaccine comparison. This makes the measure narrower than infection from any influenza strain.

A participant count is a binary outcome at the participant level: each person either meets the endpoint definition during the specified period or does not. Comparing the proportion meeting that definition between randomized groups can summarize the difference in observed event frequency. In general, binary clinical outcomes are useful when the question concerns whether an event occurred, rather than how much a continuous measure changed.

The primary endpoint was assessed in the Per Protocol Population. That population definition matters because the result pertains to participants included under that analysis population, not automatically to every person enrolled. The registry record does not report the detailed criteria used to define the Per Protocol Population or how participants with missing endpoint information were handled.

In the posted primary results, the event count was zero in the MEDI3250 group and one in the placebo group. With so few observed events, the point estimate alone is not enough to characterize the uncertainty. The confidence interval is especially important: it indicates how imprecisely the comparative effect is estimated when the observed event information is sparse.

7. Results Posted in the Registry

• MEDI3250: 0.0% (0/849) versus 0.2% (1/430) on control; risk difference -0.2 percentage points (95% CI -0.7 to 0.2); unadjusted two-proportion z-test p = 0.160.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

the Incidence of Laboratory-confirmed Influenza Infection (Any Strain)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • MEDI3250: 19.9% (169/849) versus 27.4% (118/430) on control; risk difference -7.5 percentage points (95% CI -12.5 to -2.5), risk ratio 0.73 (0.59–0.89); unadjusted two-proportion z-test p = 0.002.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for MEDI3250 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry reports two secondary outcomes: laboratory-confirmed influenza infection from any strain, and matched-strain infection by strain. The any-strain outcome is broader than the primary matched-strain endpoint. It therefore provides a complementary view of infections during surveillance, rather than a direct re-estimation of the primary question. The posted results show a different pattern of event frequency across these endpoint definitions, but the endpoint definitions must remain separate when interpreting the evidence.

The sponsor’s any-strain analysis reports vaccine efficacy of 27.5%, with a 95% confidence interval from 7.4 to 43.0. The unadjusted recalculation for that outcome has a risk difference of -0.075, a 95% confidence interval from -0.125 to -0.025, and p = 0.002. These values describe the secondary any-strain comparison. They do not remove the uncertainty in the primary matched-strain estimate, where the observed event count was much smaller.

The registry also lists matched-strain infection by strain as a secondary outcome, but further results for that outcome are not reported in the registry record. The posted information therefore does not support a detailed assessment of how individual strains contributed to the overall matched-strain result.

Unadjusted secondary findings generally carry less inferential weight when multiple outcomes are examined, because the chance of observing at least one apparently notable result can increase as more comparisons are made. This is a general statistical concern, not a claim about what happened in this trial. The registry record does not report a multiplicity adjustment or a detailed testing hierarchy. The secondary p-value should therefore be read as unadjusted, and not as though it came from a confirmed multiplicity-controlled analysis.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• the Incidence of Laboratory-confirmed Influenza Infection (Any Strain)
• the Incidence of Laboratory-confirmed Influenza Infection (Matched Strain, by Strain)

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports a binary primary outcome: whether a participant had a laboratory-confirmed matched-strain influenza infection during the surveillance period. For a binary outcome, an event proportion is the number of participants with the event relative to the number analyzed. A group comparison can express the difference between those proportions, or use another effect measure. The posted recalculation uses a risk difference, while the sponsor reports vaccine efficacy from an exact conditional method.

What does the risk difference express?

In general, a risk difference subtracts the comparator group’s event proportion from the intervention group’s event proportion. A value below zero means the observed event proportion was lower in the intervention group; a value above zero means it was higher. The primary recalculated estimate is -0.002. Its confidence interval ranges from -0.007 to 0.002, so it includes zero. That interval is consistent with uncertainty about the direction and size of the difference in the underlying event proportions.

This recalculation is unadjusted: it uses the posted group counts without adjustment for other variables. It is not a replacement for the sponsor’s analysis, which uses an exact conditional method. The two methods can produce different estimates and intervals, particularly with sparse data. The registry reports no discrepancy between the posted analysis and the recalculation.

Why does a zero-event group matter?

General statistical explanation: when one group has no observed events, methods that rely on ordinary large-sample approximations may be unreliable, because the data provide little direct information about that group’s event rate. Exact methods can be used to handle sparse event patterns, but the resulting interval may still be very wide. Here, the primary analysis has zero events in the MEDI3250 group and one in the placebo group. The sponsor’s exact conditional interval for vaccine efficacy is correspondingly broad, from -1875.3 to 100.0.

Vaccine efficacy is a relative-effect measure, and its estimate can be sensitive to very small event counts. A boundary estimate such as 100.0% does not mean the underlying effect has been established with precision. The interval communicates that substantial uncertainty remains. The record gives no sponsor p-value for this primary analysis.

How should the p-values be read?

General statistical explanation: a p-value describes how compatible the observed data are with a specified null model, under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The unadjusted recalculated primary p-value is 0.16. It should be considered alongside the point estimate, the confidence interval and the sparse event counts, rather than as a standalone verdict.

The secondary any-strain comparison has an unadjusted recalculated p-value of 0.002. It addresses a separate endpoint with a different event definition. Because the registry record does not report a multiplicity strategy, this p-value does not establish how the result would fare under any adjustment for testing multiple outcomes.

What are the planning illustrations?

General statistical explanation: sample-size planning uses assumptions about event frequency, effect size, significance level and allocation to estimate the number of participants needed for a target power. Such estimates are planning illustrations, not measurements of the trial’s observed power and not evidence that the original study was designed with those assumptions. The record’s illustration uses the observed effect and states a two-sided significance level of 0.05, equal allocation, and a normal approximation. It considers planning for 100%, 75% and 50% of the observed effect.

The resulting planning values are participants per arm for 80% power and participants per arm for 90% power. For 100% of the observed effect, the values are 499 and 667; for 75%, they are 911 and 1,219; for 50%, they are 2,103 and 2,814. These values are illustrations based on the any-strain secondary effect, not observed results and not evidence of the trial’s original design rationale. The registry record does not report a sample-size justification for the trial itself.

11. Confidence Intervals and Precision

Confidence intervals describe uncertainty around an estimated effect. In general, a narrower interval indicates greater precision, while a wider interval indicates less precision. An interval that includes zero for a risk difference leaves open the possibility of no difference in the underlying event proportions, as well as effects in either direction that fall within the interval.

For the primary matched-strain outcome, the recalculated risk difference is -0.002, with a 95% confidence interval from -0.007 to 0.002. Because the interval includes zero, the data do not pin down the direction of the risk difference. The primary event counts—zero in the MEDI3250 group and one in the placebo group—help explain why the estimate is imprecise. Sparse events can yield wide uncertainty even when the point estimate is at an extreme.

The sponsor’s primary vaccine-efficacy estimate is 100.0%, but its 95% confidence interval extends from -1875.3 to 100.0. The point estimate and interval must be read together. The boundary estimate does not convey that the effect is known precisely; the interval instead shows substantial uncertainty under the reported exact conditional method.

The any-strain secondary outcome has a recalculated risk difference of -0.075, with a 95% confidence interval from -0.125 to -0.025. The interval lies below zero, but it pertains to the broader any-strain endpoint, not the primary matched-strain endpoint. These intervals are not interchangeable, and the secondary result does not narrow the uncertainty around the primary estimate.

Confidence intervals reflect sampling uncertainty under the method used; they do not account for every possible source of bias or uncertainty in study conduct. The registry record does not provide further information about missing endpoint data, protocol deviations or sensitivity analyses that could clarify how those issues affect precision.

12. Analyses Reported by the Sponsor

For the primary endpoint, the sponsor reports vaccine efficacy of 100.0%, with a 95% confidence interval from -1875.3 to 100.0, using an exact conditional method. The unadjusted recalculation expresses the comparison as a risk difference of -0.002, with a 95% confidence interval from -0.007 to 0.002 and p = 0.16. The measures and methods differ, so their numerical estimates are not directly interchangeable. Both should be read in light of the primary counts: zero events in the MEDI3250 group and one in the placebo group.

The very broad sponsor interval signals that the exact conditional estimate is highly uncertain. The recalculated interval includes zero and likewise does not establish a precise difference. The record indicates no discrepancy between the sponsor result and the recalculation; the recalculation is a simple unadjusted comparison from the posted summary counts and does not supersede the sponsor’s analysis.

For the secondary any-strain endpoint, the sponsor reports vaccine efficacy of 27.5%, with a 95% confidence interval from 7.4 to 43.0. This is also an exact conditional analysis, and it concerns a different endpoint. The registry record does not report a sponsor p-value for either reported exact conditional analysis. Interpretation should distinguish the sponsor’s reported analyses from the unadjusted recalculations and account for the different endpoints and methods.

13. Multiplicity, Missing Data and Analysis Populations

The record identifies a primary endpoint and lists secondary outcomes, but a multiplicity strategy is not reported in the registry record. It is therefore not possible to determine from the record whether the sponsor planned to adjust for testing multiple outcomes, whether a hierarchical testing order was used, or how secondary findings were intended to contribute to confirmatory conclusions. The unadjusted secondary p-value should be interpreted with that limitation in mind.

The primary analysis population is identified as the Per Protocol Population. The registry record does not report the detailed eligibility criteria for that population, the number excluded from it, or the reasons for exclusion. The secondary outcome analysis population is not reported in the registry record. The primary results should therefore be understood as applying to the stated Per Protocol Population, without assuming that the same population definition was used for every other outcome.

Missing-data handling is not reported in the registry record. The record does not describe whether any participants lacked outcome measurements, how such cases were handled, or whether sensitivity analyses assessed alternative assumptions. Those details matter because missing endpoint information can affect both event proportions and the interpretation of uncertainty.

Other statistical planning details are also not reported in the registry record. This includes a sample-size justification for the trial, details of any interim analyses, and a complete statistical analysis plan. The registry does include a planning illustration based on an observed secondary effect, but that is not a substitute for a report of the trial’s original design assumptions.

These reporting gaps do not show that particular procedures were or were not used. They mean that the registry record does not permit an independent assessment of those procedures. Interpretation should remain anchored to the posted endpoint definitions, analysis populations and results, while recognizing that the unreported details limit evaluation of the analysis strategy.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0.01% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hydronephrosis (0.2%), pneumonia (0.2%), osteochondrosis (0.2%), appendicitis (0.1%), peritonsillar abscess (0.1%).

The safety record lists serious adverse events in 3 participants at risk in the MEDI3250 group and 3 in the placebo group. The reported at-risk counts are 868 and 433, respectively. The record also lists other adverse events in 126 MEDI3250 participants and 67 placebo participants. These are posted counts, not estimates of causal effects.

The record lists a total number of 6 serious adverse events among 1301 at risk and 193 other adverse events among 1301 at risk. Serious-event terms listed include Hydronephrosis, Pneumonia and Osteochondrosis, each at 0.2%, and Appendicitis, Peritonsillar abscess and Convulsion, each at 0.1%. The percentages and counts should be understood as the registry reports them; they do not establish whether an event was caused by the intervention.

The safety denominators differ from the primary efficacy analysis counts, which come from the Per Protocol Population. They refer to a separate reported context and should not be substituted for the primary endpoint denominators. Deaths are not reported in the registry record. The posted safety figures alone do not provide information about event timing, severity beyond the serious classification, relatedness assessment or comparative statistical testing.

15. What the Result Does, and Does Not, Mean

The primary result describes a rare observed event pattern: no matched-strain infections were recorded in the MEDI3250 group, and one was recorded in the placebo group in the Per Protocol Population. The sponsor’s estimated vaccine efficacy is 100.0%, but its confidence interval is extremely broad. The unadjusted risk-difference interval includes zero. Together, these features mean that the primary result is highly imprecise; the point estimate should not be treated as a precise measure of the underlying comparative effect.

The any-strain secondary result concerns a broader endpoint and has more observed events. Its sponsor estimate and unadjusted recalculation suggest a different level of precision than the primary matched-strain comparison. However, it answers a different question. It does not convert the sparse primary evidence into a precise matched-strain estimate, nor does it establish that the same pattern applies to each strain.

These findings do not establish that MEDI3250 does or does not work. They describe the posted results and the uncertainty around the comparisons reported in the registry. The primary confidence interval, the endpoint definitions, the analysis population and the lack of reported multiplicity details all matter when assessing what can be concluded from the record.

The safety counts provide a descriptive account of serious and other adverse events in the reported safety groups. They do not, by themselves, determine whether events were caused by treatment or establish a complete comparative safety profile. The registry record does not report deaths or provide the additional details needed to assess event timing, relatedness or missing safety information.

Overall, the record supports a cautious statistical reading: the primary endpoint had very few events and a broad interval, while the secondary any-strain analysis had a more informative event pattern but remains a secondary, unadjusted result. The registry information should not be extended beyond these reported outcomes and populations.

16. Why This Trial Matters Statistically

This trial illustrates why an extreme point estimate can coexist with substantial uncertainty. With zero primary events in one group and one in the other, the sponsor’s estimate reaches 100.0%, yet its confidence interval ranges from -1875.3 to 100.0. The interval, rather than the point estimate alone, reveals how little precision the sparse primary data provide.

It also shows why endpoint definition matters. The primary outcome is limited to laboratory-confirmed infections from matched strains, whereas the secondary any-strain outcome covers a broader set of infections. The two results answer different questions and have different observed event patterns. Statistical interpretation should not treat a broader secondary endpoint as interchangeable with the primary endpoint.

The record further distinguishes sponsor analyses from simple recalculations. The sponsor used an exact conditional method for vaccine efficacy; the recalculated risk differences are unadjusted comparisons based on posted summary counts. Each communicates the data in a different way, and neither should be read without its method and uncertainty.

Finally, the record highlights the importance of transparent reporting of multiplicity, analysis populations, missing-data handling and design assumptions. Without those details, readers cannot fully evaluate how the analysis strategy was planned or how robust the results are to alternative choices. The planning illustration is useful for understanding how assumptions about effect size relate to sample-size requirements, but it does not establish the rationale for the trial’s enrollment.

17. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary endpoint is based on only one observed event across the reported analysis groups. This makes the comparative estimate particularly sensitive to small changes in event counts and limits precision. The sponsor’s very broad confidence interval is a direct indication of that uncertainty. The primary analysis is also specified for the Per Protocol Population, and the registry record does not report the detailed criteria for that population or the results in other analysis populations.

The posted information does not describe missing endpoint data or how such data were handled. It also does not report protocol deviations, sensitivity analyses or further information about the laboratory-confirmation process. These omissions limit assessment of how robust the endpoint results are to analysis and measurement choices.

There is no reported multiplicity strategy for the secondary outcomes. The any-strain finding is therefore an unadjusted secondary result, and its inferential weight is limited by the absence of registry detail about the testing plan. Results by matched strain are not reported in the registry record, restricting assessment of variation across strains.

The safety record is descriptive and does not report deaths. It does not provide, in the information recorded, the timing or relatedness of adverse events, or a statistical comparison of safety outcomes. The efficacy and safety group counts differ, so the denominators should be interpreted within their respective analysis contexts.

Finally, the registry record does not report the trial’s sample-size justification, interim analyses or complete statistical analysis plan. These gaps constrain independent evaluation of the design and analysis choices and should be kept separate from the observed results themselves.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Phase3 Study to Evaluate the Efficacy and Safety of MEDI3250 in Healthy Japanese Children Age 7 Years Through 18 Years — NCT02269475.
• Registry record last updated 2017-04-04; status last verified 2017-02.
• Results first posted 2015-12-03.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

21. Record Summary

The registry describes a completed, randomized, double-blind, parallel-group Phase 3 study of MEDI3250 nasal spray versus placebo nasal spray in healthy Japanese children aged 7 years through 18 years. Enrollment was 1369. The primary endpoint was laboratory-confirmed influenza infection from a matched strain through the end of the surveillance period, up to end Apr (6 months), in the Per Protocol Population.

The primary analysis recorded zero events in the MEDI3250 group and one in the placebo group. The sponsor reported vaccine efficacy of 100.0%, with a 95% confidence interval from -1875.3 to 100.0; the unadjusted risk-difference recalculation was -0.002, with a 95% confidence interval from -0.007 to 0.002. These estimates are highly imprecise. The secondary any-strain result is a separate endpoint and is reported with an unadjusted p-value. Multiplicity and missing-data procedures are not reported in the registry record.